Mechanisms underlying helper T-cell plasticity: Implications for immune-mediated disease

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 5; pp. 1276 - 1287
• Main Authors: Hirahara, Kiyoshi, Poholek, Amanda, Vahedi, Golnaz, Laurence, Arian, Kanno, Yuka, Milner, Joshua D., O’Shea, John J.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.2013; Elsevier; Elsevier Limited
• Subjects: allergic disease; Allergy and Immunology; Asthma; Binding sites; Biological and medical sciences; Biology; CD4-positive T-lymphocytes; Chronic obstructive pulmonary disease, asthma; cytokines; Cytokines - biosynthesis; Cytokines - genetics; Deoxyribonucleic acid; Disease; DNA; Epigenetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Gene Expression Regulation - immunology; Genomes; histone modification; homeostasis; Humans; Immune system; Immune System Diseases - etiology; Immune System Diseases - immunology; Immune System Diseases - pathology; Immunopathology; Influence; Kinases; Ligands; Lymphocytes; Medical sciences; Metabolism; Models, Immunological; Mutation; Pneumology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Studies; T-cell plasticity; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; therapy; Transcription factors; T-cell plasticity; histone modification; HIF; therapy; H3K4me3; Treg; asthma; PU.1; T-bet; epigenetics; Rorγt; Bcl6; TFH; mTOR; allergic disease; Foxp3; IRF; mTORC; H3K27me3; Histone 3 lysine 4 trimethylation; Forkhead box protein 3; Follicular helper T; Regulatory T; B-cell lymphoma 6; T FH; Retinoic acid receptor–related orphan receptor γt; Histone 3 lysine 27 trimethylation; Mammalian target of rapamycin; Hypoxia-inducible factor; SFFV proviral integration 1; T-box transcription factor; Interferon regulatory factor; Mammalian target of rapamycin complex; Lung disease; Allergy; Immunopathology; Modification; Respiratory disease; Helper cell; Mechanism; Asthma; Immunology; Treatment; Etiology; T-Lymphocyte; Plasticity; Epigenetics; Bronchus disease; Obstructive pulmonary disease; Histone
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.03.015

CD4 helper T cells are critical for proper immune cell homeostasis and host defense but are also major contributors to immune and inflammatory disease. Arising from a simple biphasic model of differentiation (ie, TH1 and TH2 cells). A bewildering number of fates seem possible for helper T cells. To what extent different helper cell subsets maintain their characteristic gene expression profiles or exhibit functional plasticity is a hotly debated topic. In this review we will discuss how the expression of “signature cytokines” and “master regulator” transcription factors do not neatly conform to a simple helper T-cell paradigm. Although this might seem confusing, the good news is that the newly recognized complexity fits better with our understanding of immunopathogenesis. Finally, we will discuss factors, including epigenetic regulation and metabolic alterations, that contribute to helper cell specificity and plasticity.